SBIR Phase II: Design optimization and manufacturing scale-up of oral dosages with environmentally responsive polymers

这个小型企业创新研究（SBIR）第二阶段项目的更广泛的影响/商业潜力扩大了对制药产品中环境响应材料的理解和应用。目前非活性成分的局限性导致30%的新药被终止，大约一半的批准药物产品有改善疗效的空间。因此，更有效的材料对于通过处方药继续改善公共健康至关重要。作为一个规避风险的行业，制药创新优先考虑解决疾病的活性成分。然而，该项目可以证明，创新的非活性成分可以提高药物产品的功效，而对临床转化和商业化的额外风险最小。本项目将在FDA新型辅料审查计划的监管指导下，推进制剂设计，以有效纳入响应性材料和相应的生产实践，从而满足质量标准。这些发展可以建立更高的药物性能标准。广泛相容的材料可以作为一种高效的药物递送技术，其影响是更快和更相容的药物制造过程。潜在的好处将是更广泛地提供价格更低的处方药。该拟定项目有两个主要目标：（1）分别建立用于利用新型环境响应性聚合物的制剂生产和质量控制的放大生产工艺和相关分析方法，以及（2）使用相同聚合物设计有效且货架稳定的药物氟维司群胶囊制剂。主要障碍包括将目前的实验室规模的制造协议转换为与商业规模的制造设备兼容，并确保胶囊制剂在保持高效口服药物递送指标的同时具有货架稳定性。为了克服这些挑战，研发计划将首先验证制剂中间体关键质量属性的分析方法，然后在生产规模扩大和氟维司群胶囊设计期间实施。 这些目标将有助于确定平衡低运营成本和高性能指标的工艺参数和配方组成。最终的成果将是一个药物主文件（DMF），总结了使用环境响应聚合物的药物产品的生产和质量控制过程。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project expands the understanding and application of environmentally responsive materials in pharmaceutical products. The limitations of current inactive ingredients cause 30% of new drugs to be terminated and leave roughly half of approved drug products with room for improved efficacy. Thus, more effective materials are vital to continue improving public health via prescription drugs. As a risk-averse industry, pharmaceutical innovation prioritizes the active ingredients that address disease. However, this project could demonstrate that innovative inactive ingredients can enhance drug product efficacy with minimal additional risk to clinical translation and commercialization. This project will progress drug product design to effectively incorporate responsive materials and corresponding manufacturing practices to meet quality standards, with regulatory guidance from the FDA Novel Excipient Review Program. These developments could establish higher standards of drug performance. The impact of a broadly compatible material which can serve as a highly effective drug delivery technology is faster and more compatible drug manufacturing process. The potential benefit will be broader availability of prescription drugs with lower prices. The proposed project has two primary objectives: (1) establish a scaled-up manufacturing process and associated analytical methods for the production and quality control, respectively, of drug products utilizing a novel environmentally responsive polymer, and (2) design an effective and shelf-stable capsule formulation for the drug fulvestrant using the same polymer. The primary hurdles include converting current lab-scale manufacturing protocols to be compatible with commercial-scale manufacturing equipment and ensuring the capsule formulation is shelf-stable while retaining highly effective oral drug delivery metrics. To overcome these challenges, the research and development plan will first validate analytical methods for critical quality attributes of drug product intermediates, which will then be implemented during manufacturing scale-up and fulvestrant capsule design. These goals will help identify processing parameters and formulation composition that balance low operating expense and high-performance metrics. The final deliverable will be a drug master file (DMF) summarizing the manufacturing and quality control processes for drug products utilizing an environmentally responsive polymer.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.